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AZD2171 + Chemotherapy in Advanced NSCLC, Colorectal Cancer, or Other Cancer Suitable for Treatment With Capecitabine (Non-Small Lung Cancer Patients Closed to Enrollment as 8/9/07)

Phase 1
Completed
Conditions
Lung Cancer
Colorectal Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Interventions
Registration Number
NCT00107250
Lead Sponsor
NCIC Clinical Trials Group
Brief Summary

RATIONALE: AZD2171 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as paclitaxel, carboplatin, or capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving AZD2171 together with chemotherapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of AZD2171 when given together with chemotherapy in treating patients with advanced non-small cell lung cancer (closed to enrollment as of 8/9/07), colorectal cancer, or other cancer suitable to capecitabine treatment.

Detailed Description

OBJECTIVES:

* Determine the maximum tolerated dose and recommended phase II dose of AZD2171 when administered in combination with standard chemotherapy comprising either paclitaxel and carboplatin OR capecitabine in patients with advanced incurable non-small cell lung cancer (closed to accrual as of 8/9/07), colorectal cancer, or other tumor types suitable for treatment with capecitabine.

* Determine the safety and tolerability of these regimens in these patients.

* Determine the toxicity profile and dose-limiting toxic effects of these regimens in these patients.

* Determine the pharmacokinetic profile of these regimens in these patients.

* Correlate the toxicity profile with the pharmacokinetic profile of these regimens in these patients.

* Determine the antitumor activity of these regimens in patients with measurable disease.

* Correlate patient outcome (response) with baseline (using tumor samples) and serial (using urine and plasma samples) biomarkers in patients treated with these regimens.

OUTLINE: This is an open-label, multicenter, dose-escalation study of AZD2171. Patients are assigned to 1 of 2 treatment groups according to diagnosis.

* Group 1 (non-small cell lung cancer) (closed to accrual as of 8/9/07): Patients receive paclitaxel IV and carboplatin IV on day 1. Patients also receive oral AZD2171 once daily on days 2-21 of course 1 and on days 1-21 of all subsequent courses. Treatment with paclitaxel and carboplatin repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Treatment with AZD2171 repeats every 21 days in the absence of disease progression or unacceptable toxicity.

* Group 2 (colorectal or other tumor types): Patients receive oral capecitabine twice daily on days 1-14. Patients also receive oral AZD2171 once daily on days 8-21 of course 1 and on days 1-21 of all subsequent courses. Treatment with capecitabine repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Treatment with AZD2171 repeats every 21 days in the absence of disease progression or unacceptable toxicity.

In both groups, patients achieving a complete response (CR) OR a stable partial response (SPR) receive 2 additional courses beyond CR or SPR.

Cohorts of 3-6 patients per group receive escalating doses of AZD2171 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Up to 30 additional patients (20 in group 1 and 10 in group 2) will be treated at the MTD.

After completion of study treatment, patients are followed at 4 weeks and then every 3 months until disease relapse.

PROJECTED ACCRUAL: A total of 3-35 patients will be accrued for this study.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
50
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
AZD2171 + Standard chemotherpay regimenspaclitaxel-
AZD2171 + Standard chemotherpay regimenscapecitabine-
AZD2171 + Standard chemotherpay regimenscediranib maleate-
AZD2171 + Standard chemotherpay regimenscarboplatin-
Primary Outcome Measures
NameTimeMethod
Dose limiting toxicityEach dose level

To recommend phase II dose of AZD2171 when given orally daily in combination with standard chemotherapy in patients with advanced NSCLC or colon cancer or other tumour types suitable for treatment with capecitabine.

Secondary Outcome Measures
NameTimeMethod
Anti-tumour activityEach dose level

Assessing the anti-tumour activity of AZD2171 in combination with standard chemotherapy regimens in patients with measurable disease.

SafetyEach dose level

safety, tolerability, toxicity profile, dose limiting toxicities and pharmacokinetic profile of AZD2171 and standard chemotherapy given in these combinations. The correlation, if any,between the toxicity profile and the pharmacokinetics will be determined.

Tumour ResponseEach dose level

To correlate patient outcomes (response) with baseline (tumour) and serial (urine and plasma) biomarkers

Trial Locations

Locations (2)

Ottawa Hospital Regional Cancer Centre - General Campus

🇨🇦

Ottawa, Ontario, Canada

Princess Margaret Hospital

🇨🇦

Toronto, Ontario, Canada

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